Genetic Variant RXFP2:p.Gly72Glu (chr13-31758378-G-A) – ACMG Classification: Uncertain_significance (1 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2BP4

The NM_130806.5(RXFP2):c.215G>A(p.Gly72Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000274 in 1,461,858 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000027 ( 0 hom. )

Consequence

RXFP2
NM_130806.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.919

Publications

0 publications found

Variant links:

Genes affected

RXFP2 (HGNC:17318): (relaxin family peptide receptor 2) This gene encodes a member of the GPCR (G protein-coupled, 7-transmembrane receptor) family. Mutations in this gene are associated with cryptorchidism. Alternatively spliced transcript variants encoding different isoforms have been found for this gene.[provided by RefSeq, Oct 2009]

RXFP2 Gene-Disease associations (from GenCC):

cryptorchidism
Inheritance: AR Classification: LIMITED Submitted by: Ambry Genetics

RXFP2 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.26888487).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein
RXFP2	NM_130806.5 link	c.215G>A	p.Gly72Glu	missense_variant	Exon 2 of 18	ENST00000298386.7	NP_570718.1
RXFP2	NM_001166058.2 link	c.215G>A	p.Gly72Glu	missense_variant	Exon 2 of 17		NP_001159530.1
RXFP2	XM_017020389.2 link	c.215G>A	p.Gly72Glu	missense_variant	Exon 2 of 15		XP_016875878.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RXFP2	ENST00000298386.7 link	c.215G>A	p.Gly72Glu	missense_variant	Exon 2 of 18	1	NM_130806.5	ENSP00000298386.2		Q8WXD0-1
RXFP2	ENST00000380314.2 link	c.215G>A	p.Gly72Glu	missense_variant	Exon 2 of 17	1		ENSP00000369670.1		Q8WXD0-2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.00000398

AC:

AN:

251354

AF XY:

0.00000736

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000880

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000274

AC:

AN:

1461858

Hom.:

Cov.:

AF XY:

0.00000275

AC XY:

AN XY:

727238

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33478

American (AMR)

AF:

0.00

AC:

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26136

East Asian (EAS)

AF:

0.00

AC:

AN:

39700

South Asian (SAS)

AF:

0.00

AC:

AN:

86258

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53418

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5766

European-Non Finnish (NFE)

AF:

0.00000360

AC:

AN:

1111984

Other (OTH)

AF:

0.00

AC:

AN:

60394

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.525

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

Alfa

AF:

0.0000468

Hom.:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Apr 07, 2022

Ambry Genetics

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:clinical testing

The c.215G>A (p.G72E) alteration is located in exon 2 (coding exon 2) of the RXFP2 gene. This alteration results from a G to A substitution at nucleotide position 215, causing the glycine (G) at amino acid position 72 to be replaced by a glutamic acid (E). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.13

BayesDel_addAF

Uncertain

0.11

BayesDel_noAF

Uncertain

-0.080

CADD

Benign

(source)

DANN

Benign

0.96

DEOGEN2

Benign

0.36

.;T

Eigen

Benign

-0.20

Eigen_PC

Benign

-0.011

FATHMM_MKL

Uncertain

0.85

LIST_S2

Benign

0.79

T;T

M_CAP

Benign

0.028

MetaRNN

Benign

0.27

T;T

MetaSVM

Uncertain

0.037

MutationAssessor

Benign

0.63

N;N

PhyloP100

0.92

PrimateAI

Uncertain

0.63

PROVEAN

Uncertain

-2.5

N;N

REVEL

Uncertain

0.34

Sift

Benign

0.63

T;T

Sift4G

Benign

0.85

T;T

Polyphen

0.011

.;B

Vest4

0.38

MutPred

0.50

Gain of catalytic residue at K68 (P = 0.0037);Gain of catalytic residue at K68 (P = 0.0037);

MVP

0.80

MPC

0.23

ClinPred

0.20

GERP RS

5.5

Varity_R

0.25

gMVP

0.50

Mutation Taster

=48/52

disease causing

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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13-31758378-G-A

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over